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Cross-talk between androgen receptor/filamin A and TrkA regulates neurite outgrowth in PC12 cells
Steroids and growth factors control neuronal development through their receptors under physiological and pathological conditions. We show that PC12 cells harbor endogenous androgen receptor (AR), whose inhibition or silencing strongly interferes with neuritogenesis stimulated by the nonaromatizable...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4571344/ https://www.ncbi.nlm.nih.gov/pubmed/26063730 http://dx.doi.org/10.1091/mbc.E14-09-1352 |
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author | Di Donato, Marzia Bilancio, Antonio D'Amato, Loredana Claudiani, Pamela Oliviero, Maria Antonietta Barone, Maria Vittoria Auricchio, Alberto Appella, Ettore Migliaccio, Antimo Auricchio, Ferdinando Castoria, Gabriella |
author_facet | Di Donato, Marzia Bilancio, Antonio D'Amato, Loredana Claudiani, Pamela Oliviero, Maria Antonietta Barone, Maria Vittoria Auricchio, Alberto Appella, Ettore Migliaccio, Antimo Auricchio, Ferdinando Castoria, Gabriella |
author_sort | Di Donato, Marzia |
collection | PubMed |
description | Steroids and growth factors control neuronal development through their receptors under physiological and pathological conditions. We show that PC12 cells harbor endogenous androgen receptor (AR), whose inhibition or silencing strongly interferes with neuritogenesis stimulated by the nonaromatizable synthetic androgen R1881 or NGF. This implies a role for AR not only in androgen signaling, but also in NGF signaling. In turn, a pharmacological TrkA inhibitor interferes with NGF- or androgen-induced neuritogenesis. In addition, androgen or NGF triggers AR association with TrkA, TrkA interaction with PI3-K δ, and downstream activation of PI3-K δ and Rac in PC12 cells. Once associated with AR, filamin A (FlnA) contributes to androgen or NGF neuritogenesis, likely through its interaction with signaling effectors, such as Rac. This study thus identifies a previously unrecognized reciprocal cross-talk between AR and TrkA, which is controlled by β1 integrin. The contribution of FlnA/AR complex and PI3-K δ to neuronal differentiation by androgens and NGF is also novel. This is the first description of AR function in PC12 cells. |
format | Online Article Text |
id | pubmed-4571344 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-45713442015-10-16 Cross-talk between androgen receptor/filamin A and TrkA regulates neurite outgrowth in PC12 cells Di Donato, Marzia Bilancio, Antonio D'Amato, Loredana Claudiani, Pamela Oliviero, Maria Antonietta Barone, Maria Vittoria Auricchio, Alberto Appella, Ettore Migliaccio, Antimo Auricchio, Ferdinando Castoria, Gabriella Mol Biol Cell Articles Steroids and growth factors control neuronal development through their receptors under physiological and pathological conditions. We show that PC12 cells harbor endogenous androgen receptor (AR), whose inhibition or silencing strongly interferes with neuritogenesis stimulated by the nonaromatizable synthetic androgen R1881 or NGF. This implies a role for AR not only in androgen signaling, but also in NGF signaling. In turn, a pharmacological TrkA inhibitor interferes with NGF- or androgen-induced neuritogenesis. In addition, androgen or NGF triggers AR association with TrkA, TrkA interaction with PI3-K δ, and downstream activation of PI3-K δ and Rac in PC12 cells. Once associated with AR, filamin A (FlnA) contributes to androgen or NGF neuritogenesis, likely through its interaction with signaling effectors, such as Rac. This study thus identifies a previously unrecognized reciprocal cross-talk between AR and TrkA, which is controlled by β1 integrin. The contribution of FlnA/AR complex and PI3-K δ to neuronal differentiation by androgens and NGF is also novel. This is the first description of AR function in PC12 cells. The American Society for Cell Biology 2015-08-01 /pmc/articles/PMC4571344/ /pubmed/26063730 http://dx.doi.org/10.1091/mbc.E14-09-1352 Text en © 2015 Di Donato et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. |
spellingShingle | Articles Di Donato, Marzia Bilancio, Antonio D'Amato, Loredana Claudiani, Pamela Oliviero, Maria Antonietta Barone, Maria Vittoria Auricchio, Alberto Appella, Ettore Migliaccio, Antimo Auricchio, Ferdinando Castoria, Gabriella Cross-talk between androgen receptor/filamin A and TrkA regulates neurite outgrowth in PC12 cells |
title | Cross-talk between androgen receptor/filamin A and TrkA regulates neurite outgrowth in PC12 cells |
title_full | Cross-talk between androgen receptor/filamin A and TrkA regulates neurite outgrowth in PC12 cells |
title_fullStr | Cross-talk between androgen receptor/filamin A and TrkA regulates neurite outgrowth in PC12 cells |
title_full_unstemmed | Cross-talk between androgen receptor/filamin A and TrkA regulates neurite outgrowth in PC12 cells |
title_short | Cross-talk between androgen receptor/filamin A and TrkA regulates neurite outgrowth in PC12 cells |
title_sort | cross-talk between androgen receptor/filamin a and trka regulates neurite outgrowth in pc12 cells |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4571344/ https://www.ncbi.nlm.nih.gov/pubmed/26063730 http://dx.doi.org/10.1091/mbc.E14-09-1352 |
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